Octan-2-one

Endpoint summary

Description of key information

No signs of contact sensitization were observed at 1% ICC and 20% ACC concentrations. Hence, the test chemical was considered to be non-sensitizing to the skin of albino Hartley guinea pigs.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Data is from publication .

Qualifier:

according to guideline

Guideline:

other: Modified Draize test method.

Principles of method if other than guideline:

Modified Draize Technique was employed to determine the concentrations suitable for sensitization testing [injection challenge concentration(ICC) and application challenge concentration ( ACC) ] of the test chemical

GLP compliance:

not specified

Type of study:

Draize test

Justification for non-LLNA method:

not specified.

Species:

guinea pig

Strain:

Hartley

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS

- Weight at study initiation: 350 g
- Housing: Housed in wire mesh cages in pairs of the same sex
- Diet (e.g. ad libitum): Pelleted guinea pig diet, cabbage and hay ad libitum
- Water (e.g. ad libitum): water ad libitum

Route:

intradermal

Vehicle:

other: yes (no details mentioned)

Concentration / amount:

Induction concentration: 0.1 mL at 2.5 X 1%(ICC) : 10 guinea pigs

Day(s)/duration:

3 weeks

Adequacy of induction:

other: The concentration giving slight but perceptible irritation with no oedema was selected as the injection challenge concentration (ICC).

No.:

#1

Route:

intradermal and epicutaneous

Vehicle:

other: yes (no details mentioned)

Concentration / amount:

Challenge concentration: 0.1 mL at 1% (ICC) and 20% (ACC): 10 guinea pigs
Re- challenge concentration: 0.1 mL at 1%(ICC) and 20% (ACC): 10 guinea pigs

Day(s)/duration:

24 hours

Adequacy of challenge:

other: The concentration giving slight but perceptible irritation with no oedema was selected as the injection challenge concentration (ICC). The highest concentration which caused no irritation was selected as the application challenge concentration (ACC)

No. of animals per dose:

10 animals (4male and 6 female)

Details on study design:

RANGE FINDING TESTS: For each test material preliminary irritation tests were done in guinea pigs to determine concentrations suitable for sensitization testing.

MAIN STUDY
A. INDUCTION EXPOSURE: Intradermal
- No. of exposures:4
- Exposure period: No Data Available
- Test groups:10 guinea pigs
- Control group: No Data Available
- Site: 4 sites, 2 auxillary and 2 inguinal lymph nodes
- Frequency of applications:1
- Duration: No Data Available
- Concentrations: 0.1 mL at 2.5 X 1% (ICC)

B. CHALLENGE EXPOSURE: Intradermal and Epicutaneous
- No. of exposures:1
- Day(s) of challenge: Fourteen days later, challenge test was performed
- Exposure period:24 hours
- Test groups:10 guinea pigs
- Control group: No Data Available
- Site: onto the shaved flank in a small circular area
- Concentrations: 0.1 mL at 1% (ICC) and 20%(ACC).
- Evaluation (hr after challenge):24 hours

C. RECHALLENGE EXPOSURE
- No. of exposures:1
- Day(s) of challenge: 7 Days Later , rechalleange test was performed.
- Exposure period: No Data Available
- Test groups:10 animal
- Control group: 4 animal (same sex)
- Site: Intradermally and topically on opposite flanks
- Concentrations: 0.1 mL at 1% (ICC) and 20% (ACC).
- Evaluation (hr after challenge): No Data Available

-Other:

Observations and scoring –
Each injection reaction was given a total score based on size (2 largest diameters), erythema and oedema. Individual reactions were considered positive when their total score was significantly greater than the average total score for control reactions. Application reactions were scored on a 0 to +++ scale. Reactions were examined under a Philips colour-matching unit with 3 Philips 40 W Actinic Blue 05 fluorescent tubes and 3 Philips 40 W White 35 fluorescent tubes.

Challenge controls:

At each challenge with controls, 4 previously untreated animals of the same sex and similar weight to the test animals were treated intradermally and topically on opposite flanks with 0.1 ml aliquots of test substance at the ICC and ACC respectively.

Positive control substance(s):

not specified

Positive control results:

No data

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

0.1 ml at 1%[ICC] and 20%[ACC]

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

No skin sensitization reactions was observed at the tested concentrations

Remarks on result:

no indication of skin sensitisation

SENSITIZATION POTENTIAL OF SYNTHETIC PERFUME INGREDIENTS

Non-sensitizer = no evidence of sensitization

Test chemical	ICC(%)	ACC(%)	Results
111 -13 -7	1	20	Not sensitizer

 

Interpretation of results:

other: not sensitising

Conclusions:

No signs of contact sensitization were observed at 1% ICC and 20% ACC concentrations. Hence, the test chemical was considered to be non-sensitizing to the skin of albino Hartley guinea pigs..

Executive summary:

Modified Draize Technique was employed to determine the concentrations suitable\ for sensitization testing [injection challenge concentration(ICC) and application challenge concentration ( ACC) ] of the test chemical

Hartley strain albino guinea pigs bred were used for the study. Four guinea pigs of same sex were used for the preliminary irritation study and 10 guinea pigs were used for the main sensitization studyand 4 previously untreated animals of the same sexwere used as challenge controls.

The preliminary irritation tests were done in guinea pigs to determine concentrations suitable for sensitization testing [injection challenge concentration(ICC) and application challenge concentration(ACC) ]

The ICC and ACC for the test chemical was determined to be 1% and 20% respectively

In the induction phase, 0.1 ml aliquots of test substance at 2.5 times the ICC were injected intradermally at 4 sites which overlie the 2 auxillary and 2 inguinal lymph nodes. After a rest period of 14 days, each animal was challenged

intradermally in one flank and topically in the other with 0.1 ml aliquots of test substance at the respective ICC and ACC: the topical application was made by spreading 0.1 ml of the test substance onto the shaved flank in a small circular area which was not covered. Twenty-four hours later the reactions were scored and apparent sensitization reactions confirmed 7 days later by a second challenge with controls included.At each challenge with controls, 4 previously untreated animals of the same sex were treated intradermally and topically on opposite flanks with 0.1 ml aliquots of test substance at the ICC and ACC respectively.

 

Individual reactions were considered positive when their total score was significantly greater than the average total score for control reactions. Application reactions were scored on a 0 to +++ scale and individual reactions were considered positive if (a) they were + or greater and (b) there were no erythema reactions in controls.

 

No signs of contact sensitization were observed at 1% ICC and 20% ACC concentrations. Hence, the test chemical ewas considered to be non-sensitizingto the skin of albino Hartley guinea pigs.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Various studies were reviewed to determine the extent of dermal sensitization caused by the test chemical in living organisms. These include in vivo experiments performed on guinea pigs, humans as well as estimated data for the test chemical. The results are summarized below:

Modified Draize Technique was employed to determine the concentrations suitable\ for sensitization testing [injection challenge concentration(ICC) and application challenge concentration ( ACC) ] of the test chemical

Hartley strain albino guinea pigs bred were used for the study. Four guinea pigs of same sex were used for the preliminary irritation study and 10 guinea pigs were used for the main sensitization studyand 4 previously untreated animals of the same sexwere used as challenge controls.

The preliminary irritation tests were done in guinea pigs to determine concentrations suitable for sensitization testing [injection challenge concentration(ICC) and application challenge concentration(ACC) ]

The ICC and ACC for the test chemical was determined to be 1% and 20% respectively

In the induction phase, 0.1 ml aliquots of test substance at 2.5 times the ICC were injected intradermally at 4 sites which overlie the 2 auxillary and 2 inguinal lymph nodes. After a rest period of 14 days, each animal was challenged intradermally in one flank and topically in the other with 0.1 ml aliquots of test substance at the respective ICC and ACC: the topical application was made by spreading 0.1 ml of the test substance onto the shaved flank in a small circular area which was not covered. Twenty-four hours later the reactions were scored and apparent sensitization reactions confirmed 7 days later by a second challenge with controls included.At each challenge with controls, 4 previously untreated animals of the same sex were treated intradermally and topically on opposite flanks with 0.1 ml aliquots of test substance at the ICC and ACC respectively. Individual reactions were considered positive when their total score was significantly greater than the average total score for control reactions. Application reactions were scored on a 0 to +++ scale and individual reactions were considered positive if (a) they were + or greater and (b) there were no erythema reactions in controls.

 No signs of contact sensitization were observed at 1% ICC and 20% ACC concentrations. Hence, the test chemical was considered to be non-sensitizing to the skin of albino Hartley guinea pigs.

This is supported by the results of a Human maximization test performed to evaluate the skin sensitizing potential of test chemical in humans. The test material 4% in petrolatum was exposed to 25 human volunteers(duration and observation period not specified) . No dermal reactions were observed in humans when tested at 4% concentration in petrolatum .Therefore test chemical was considered to be non sensitizing in human.

These results are supported by an Open Epicutaneous Test (OET) performed on guinea pigs to assess the skin sensitization potential of test chemical.

 On day 1 during induction, 0.1 ml of the test chemical was applied at concentrations of 100%, 30%, 10%, 3%, 1%, or 0.3% in vehicle to an area measuring 8 cm2 on the clipped flank skin of the guinea pigs. The applications are repeated daily for 3 weeks or done 5 times weekly during 4 weeks, usually on the same skin sites. The application sites were left uncovered and the reactions, if continuous daily applications were performed, can be read 24 h after each application, or at the end of each week.

 To determine whether or not contact sensitization was induced, all groups of guinea pigs previously treated for 21 days, as well as 10 untreated, or only pretreated with the vehicle, controls are tested on days 21 and 35 on the contralateral flank with the test material. This test was performed by applying with a pipette 0.025 ml of each concentration to skin areas measuring 2 cm2. The reactions were read after 24,48 and/or 72h.

It was observed that none of the guinea pigs induced contact sensitization at challenge concentration of 2%.Thus the test chemical was considered to be not sensitizing on skin of guinea pigs at concentration of 2% in an Open Epicutaneous Test (OET).

Skin sensitization effects were also estimated by four different models i.e, Battery, Leadscope, SciQSAR and CASE Ultra used within Danish QSAR database for the test chemical. Based on estimation, no skin sensitization reactions were observed in guinea pigs and humans. Therefore, the test chemical was considered to be not sensitizing.

The above studies are further supported by a Human maximization study performed to assess the dermal sensitization potential of the test chemical in humans. The test substance 5% in petrolatum was applied to the skin of 35 human volunteers and observed for effects. (duration, observation period not mentioned).

No sensitization was observed after to 5% test chemical in petrolatum to the skin of 35 human volunteers. Hence, the test chemical was considered to be not sensitizing to skin.

Available results for the test chemical indicate a very strong possibility that it lacks the potential to cause any dermal reaction to the skin. Hence, the test chemical can be considered to be not sensitizing to skin.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Available results for the test chemical indicate a very strong possibility that it lacks the potential to cause any dermal reaction to the skin. Hence, the test chemical can be considered to be not sensitizing to skin.